2004 Fiscal Year Final Research Report Summary
Innate immunity and expressions of TLRs during upper abdominal surgery
| Project/Area Number |
14370499
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | University of Occupational Environmental Health(UOEH) |
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Principal Investigator |
OGATA Masanori UOEH, School of medicine, associate professor, 医学部, 助教授 (70169176)
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| Co-Investigator(Kenkyū-buntansha) |
KWASAKI Takashi UOEH, School of medicine, assistant professor, 医学部, 講師 (60299633)
NANDATE Kouichiroh UOEH, University hospital, instructor, 大学病院, 助手 (50299632)
SHIGEMATSU Akio UOEH, President, 副学長 (30037428)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Toll like receptor / Innate immunit / Surgical stress / phagocytosis / Oxygen burst / Anesthesia / MIF / HSP-70 |
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| Research Abstract |
We have demonstrated that surgical stress rapidly induced transient hyporesponsiveness of blood cells to endotoxin and that monocyte mCD 14 and HLA-DR expression reduced from the early period of surgery under general anesthesia. The Toll-like receptors (TLRs) are one of the most important pattern recognition receptor families TLR2 recognizes gram-positive organism-derived pathogen-associated molecular patterns and TLR4 recognized both viral components and gram-negative LPS. The aim of this study was to examine the expressions of Toll-like receptor (TLR)-2 and 4 during surgery.
Materials & Methods
・After obtaining approval from our committee on human research and informed consents, the blood samples were obtained from the 23 patients of upper abdominal surgery before incision (Pre-OP), at 2hr after incision (OPE2h), the end of surgery (Post-OPE) and 24hr after incision(OPE24hr).
・The blood cells were incubated for 30min in the dark with a saturating concentration of fluorescein isothiocyan
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ate (FITC)-labeled monoclonal antibodies directed against TLR2, or with a saturating concentration of physoerythrin (PE)-labeled monoclonal antibodies directed against TLR4. A lysing medium was added to lyse erythrocyte, and after lysis was complete, the samples were fixed 0.2% paraformaldehyde and washed twice. All samples were analyzed immediately using flow cytometry and XL software (EPIC-XL; Beckman Culter Electronics). The results were described as the mean fluorescence intensity.
・Plasma levels of IL-10,MIF, HSP-7
Results
1. Both expression of TLR2 and TLR4 significantly decreased from OPE2h and recovered slightly at OPE24h.
2. Both of plasma IL-10 and cortisol increased significantly from OPE2h.
3. Plasma MIF increased significantly from 2h after incision. Plasma HSP-70 increased significantly at the end of an operation.
Conclusions
1) Both expressions of TLR2 and TLR4 significantly decreased at the early period of an operation.
2) Anti-inflammatory mediators such as IL-10 and cortisol may cause the decrease of TLR expressions.
3) In contrast, HSP-70 and MIF may restore the decrease of TLR expressions.
4) It should be noted that the impairment of host-defense mechanisms occurs at the early period of an operation. Less
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